Personalized Prediction of Lifetime Benefits with Statin Therapy for Asymptomatic Individuals: A Modeling Study

Background: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. Methods and Findings: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. Conclusions: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy. Please see later in the article for the Editors' Summar

Personalized Prediction of Lifetime Benefits with Statin Therapy for Asymptomatic Individuals: A Modeling Study

Background: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. Methods and Findings: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. Conclusions: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy. Please see later in the article for the Editors' Summary

Stable Atmospheric Boundary Layers and Diurnal Cycles – Challenges for Weather and Climate Models

The representation of the atmospheric boundary layer is an important part of weather and climate models and impacts many applications such as air quality and wind energy. Over the years, the performance in modeling 2-m temperature and 10-m wind speed has improved but errors are still significant. This is in particular the case under clear skies and low wind speed conditions at night as well as during winter in stably stratified conditions over land and ice. In this paper, the authors review these issues and provide an overview of the current understanding and model performance. Results from weather forecast and climate models are used to illustrate the state of the art as well as findings and recommendations from three intercomparison studies held within the Global Energy and Water Exchanges (GEWEX) Atmospheric Boundary Layer Study (GABLS). Within GABLS, the focus has been on the examination of the representation of the stable boundary layer and the diurnal cycle over land in clear-sky conditions. For this purpose, single-column versions of weather and climate models have been compared with observations, research models, and large-eddy simulations. The intercomparison cases are based on observations taken in the Arctic, Kansas, and Cabauw in the Netherlands. From these studies, we find that even for the noncloudy boundary layer important parameterization challenges remain.SB acknowledges the financial support received from the NationalScience Foundation by way of Grant AGS-1122315

Nutritional status and structural brain changes in Alzheimer's disease: The NUDAD project

INTRODUCTION: Weight loss is associated with higher mortality and progression of cognitive decline, but its associations with magnetic resonance imaging (MRI) changes related to Alzheimer's disease (AD) are unknown. METHODS: We included 412 patients from the NUDAD project, comprising 129 with AD dementia, 107 with mild cognitive impairment (MCI), and 176 controls. Associations between nutritional status and MRI measures were analyzed using linear regression, adjusted for age, sex, education, cognitive functioning, and cardiovascular risk factors. RESULTS: Lower body mass index (BMI), fat mass (FM), and fat free mass index were associated with higher medial temporal atrophy (MTA) scores. Lower BMI, FM, and waist circumference were associated with more microbleeds. Stratification by diagnosis showed that the observed associations with microbleeds were only significant in MCI. DISCUSSION: Lower indicators of nutritional status were associated with more MTA and microbleeds, with largest effect sizes in MCI

Global Intermittency and Collapsing Turbulence in the Stratified Planetary Boundary Layer

Direct numerical simulation of the turbulent Ekman layer over a smooth wall is used to investigate bulk properties of a planetary boundary layer under stable stratification. Our simplified configuration depends on two non-dimensional parameters: a Richardson number characterizing the stratification and a Reynolds number characterizing the turbulence scale separation. This simplified configuration is sufficient to reproduce global intermittency, a turbulence collapse, and the decoupling of the surface from the outer region of the boundary layer. Global intermittency appears even in the absence of local perturbations at the surface; the only requirement is that large-scale structures several times wider than the boundary-layer height have enough space to develop. Analysis of the mean velocity, turbulence kinetic energy, and external intermittency is used to investigate the large-scale structures and corresponding differences between stably stratified Ekman flow and channel flow. Both configurations show a similar transition to the turbulence collapse, overshoot of turbulence kinetic energy, and spectral properties. Differences in the outer region resulting from the rotation of the system lead, however, to the generation of enstrophy in the non-turbulent patches of the Ekman flow. The coefficient of the stability correction function from Monin-Obukhov similarity theory is estimated as (Formula presented.) in agreement with atmospheric observations, theoretical considerations, and results from stably stratified channel flows. Our results demonstrate the applicability of this set-up to atmospheric problems despite the intermediate Reynolds number achieved in our simulations. © 2014 The Author(s)

A review of African horse sickness and its implications for Ireland

African horse sickness is an economically highly important non-contagious but infectious Orbivirus disease that is transmitted by various species of Culicoides midges. The equids most severely affected by the virus are horses, ponies, and European donkeys; mules are somewhat less susceptible, and African donkeys and zebra are refractory to the devastating consequences of infection. In recent years, Bluetongue virus, an Orbivirus similar to African horse sickness, which also utilises Culicoides spp. as its vector, has drastically increased its range into previously unaffected regions in northern Europe, utilising indigenous vector species, and causing widespread economic damage to the agricultural sector. Considering these events, the current review outlines the history of African horse sickness, including information concerning virus structure, transmission, viraemia, overwintering ability, and the potential implications that an outbreak would have for Ireland. While the current risk for the introduction of African horse sickness to Ireland is considered at worst ‘very low’, it is important to note that prior to the 2006 outbreak of Bluetongue in northern Europe, both diseases were considered to be of equal risk to the United Kingdom (‘medium-risk’). It is therefore likely that any outbreak of this disease would have serious socio-economic consequences for Ireland due to the high density of vulnerable equids and the prevalence of Culicoides species, potentially capable of vectoring the virus

Assessment of vector/host contact: comparison of animal-baited traps and UV-light/suction trap for collecting Culicoides biting midges (Diptera: Ceratopogonidae), vectors of Orbiviruses

<p>Abstract</p> <p>Background</p> <p>The emergence and massive spread of bluetongue in Western Europe during 2006-2008 had disastrous consequences for sheep and cattle production and confirmed the ability of Palaearctic <it>Culicoides </it>(Diptera: Ceratopogonidae) to transmit the virus. Some aspects of <it>Culicoides </it>ecology, especially host-seeking and feeding behaviors, remain insufficiently described due to the difficulty of collecting them directly on a bait animal, the most reliable method to evaluate biting rates.</p> <p>Our aim was to compare typical animal-baited traps (drop trap and direct aspiration) to both a new sticky cover trap and a UV-light/suction trap (the most commonly used method to collect <it>Culicoides</it>).</p> <p>Methods/results</p> <p>Collections were made from 1.45 hours before sunset to 1.45 hours after sunset in June/July 2009 at an experimental sheep farm (INRA, Nouzilly, Western France), with 3 replicates of a 4 sites × 4 traps randomized Latin square using one sheep per site. Collected <it>Culicoides </it>individuals were sorted morphologically to species, sex and physiological stages for females. Sibling species were identified using a molecular assay. A total of 534 <it>Culicoides </it>belonging to 17 species was collected. Abundance was maximal in the drop trap (232 females and 4 males from 10 species) whereas the diversity was the highest in the UV-light/suction trap (136 females and 5 males from 15 species). Significant between-trap differences abundance and parity rates were observed.</p> <p>Conclusions</p> <p>Only the direct aspiration collected exclusively host-seeking females, despite a concern that human manipulation may influence estimation of the biting rate. The sticky cover trap assessed accurately the biting rate of abundant species even if it might act as an interception trap. The drop trap collected the highest abundance of <it>Culicoides </it>and may have caught individuals not attracted by sheep but by its structure. Finally, abundances obtained using the UV-light/suction trap did not estimate accurately <it>Culicoides </it>biting rate.</p